The goal of this research is to investigate factors which regulate ketoacid (acetoacetate and beta-hydroxybutyrate) mechanism in man. Concerted effort will be directed toward: 1) exploring the possibility that it is the intracellular concentrations of ketoacids and free fatty acids that regulate the preferential utilization of these competitive substrates by muscle in various nutritional and diabetic states; 2) quantifying ketoacid turnover and oxidative rates in physiologic and pathologic ketosis by applying isotope trace techniques in man during starvation and uncontrolled diabetic states; and 3) delineating the influence of hormones and energy-balance on hepatic ketogenesis by combining differences in ketoacid concentrations across the liver with hepatic blood flow before and after intraportal infusion of insulin, glucagon or alanine in intact man.